Francois Vigneault (Shape Therapeutics)

EX­CLU­SIVE: Shape Ther­a­peu­tics rais­es $112M in bid to make RNA edit­ing — and a whole lot else — a re­al­i­ty

Two years af­ter spin­ning out of CRISPR pi­o­neer Prashant Mali’s lab, Shape Ther­a­peu­tics has a lot more cash and a slight­ly new mis­sion.

The com­pa­ny orig­i­nal­ly launched in 2019 with plans to de­vel­op ther­a­pies around a new form of gene edit­ing, one they hoped could bet­ter ad­dress cer­tain dis­eases than CRISPR or oth­er forms of gene ma­nip­u­la­tions. That’s still their goal, but CEO Fran­cois Vi­gneault has added a few oth­ers in the mean­time.

“The com­pa­ny re­al­ly start­ed as, how can we find a so­lu­tion to some of the lim­i­ta­tions of gene edit­ing?” Vi­gneault said. “But from there, we quick­ly re­al­ized there was a mas­sive bot­tle­neck in an­oth­er sphere of gene ther­a­py.”

Shape end­ed up spend­ing con­sid­er­able time and re­sources try­ing to de­vel­op and make broad­ly avail­able so­lu­tions to two of the biggest con­straints that have held up the broad­er field: man­u­fac­tur­ing and de­liv­ery. They’ll now have a lot more mon­ey to do so and bring for­ward their own med­i­cines, an­nounc­ing a $112 mil­lion Se­ries B on Thurs­day led by Decheng Cap­i­tal and Bre­ton Cap­i­tal.

Shape spe­cial­izes in RNA edit­ing; the com­pa­ny tries to de­vel­op ther­a­pies that in­ter­cept the bro­ken mes­sages that the DNA of pa­tients with cer­tain dis­eases sends out and cor­rect it be­fore it gets turned in­to pro­teins. That con­trasts with CRISPR and oth­er gene edit­ing ap­proach­es that try to di­rect­ly — and per­ma­nent­ly – al­ter DNA.

It does so by ex­ploit­ing a nat­u­ral­ly oc­cur­ring en­zyme that’s al­ready present in hu­man cells called ADAR. By send­ing in their own spe­cial­ly con­struct­ed strand of guide RNA, re­searchers can in the­o­ry re­cruit this en­zyme and get it to ma­nip­u­late spe­cif­ic strands of mes­sen­ger RNA in par­tic­u­lar ways. They could, for ex­am­ple, delete or add bases.

Shape is fo­cus­ing their ef­forts on neu­rons, where ADAR seems to work par­tic­u­lar­ly well — pos­si­bly be­cause it’s nat­u­ral­ly high­ly ex­pressed — and where, by con­trast, CRISPR com­pa­nies have had par­tic­u­lar dif­fi­cul­ty ap­ply­ing their more well-known tech­nol­o­gy. They have lead pro­grams in the rare ge­net­ic dis­ease Rett syn­drome and Parkin­son’s.

In de­vel­op­ing those ther­a­pies, Vi­gneault and his col­leagues ran square in­to the prob­lems every gene ther­a­py com­pa­ny has hit dur­ing the field’s 2010s resur­gence. The vi­ral vec­tors used to shut­tle genes (or in this case, RNA) are dif­fi­cult to man­u­fac­ture at scale. And it’s dif­fi­cult to de­vel­op ones that go pre­cise­ly to the right tis­sue and the right kind of cell in hu­mans.

“We found this [tech­nol­o­gy] is a ma­jor ad­van­tage in neu­rons and CNS dis­or­ders,” Vi­gneault said. “But on the de­liv­ery front what we dis­cov­er is a huge lim­i­ta­tion.”

So Shape en­gi­neered a cell line they claim can pro­duce more ade­no-as­so­ci­at­ed virus (AAV), the most com­mon vi­ral vec­tor used in gene ther­a­py, than any oth­er method. And they in­vest­ed in the tech­nol­o­gy to en­gi­neer AAVs, screen­ing mil­lions of AAVs in cells and mon­keys to de­vel­op ones par­tic­u­lar­ly suit­ed to reach­ing neu­rons or mus­cles.

That puts Shape in di­rect com­pe­ti­tion with com­pa­nies such as Affinia and Dyno, which are ded­i­cat­ed sole­ly to AAV en­gi­neer­ing and have raised hun­dreds of mil­lions of dol­lars and signed bil­lion-dol­lar deals with Big Phar­ma for their vec­tors.

Vi­gneault said Shape will sim­i­lar­ly try to make their AAV and cell lines avail­able to oth­er groups in in­dus­try and acad­e­mia, while con­tin­u­ing to de­vel­op their own ther­a­pies in house and with larg­er com­pa­nies. They have broad am­bi­tions there, too, re­cent­ly up­dat­ing their “pipeline” on­line to show, rather than the few pro­grams clos­est to the clin­ic, a con­stel­la­tion of the dozens of dis­eases they be­lieve their ADAR tech is best suit­ed for, from Alzheimer’s to cys­tic fi­bro­sis.

“The idea is to build a slight­ly dif­fer­ent com­pa­ny than the typ­i­cal one,” Vi­gneault said. “First make a tool that’s dis­rup­tive, not an in­cre­men­tal im­prove­ment, and when you have that tool, make it avail­able so that you can help as many pa­tients as pos­si­ble be­cause one com­pa­ny can’t do it all.”

Cor­rec­tion: The ar­ti­cle has been to clar­i­fy Shape spun out of the Mali lab, not the Church lab.

A new era of treat­ment: How bio­mark­ers are chang­ing the way we think about can­cer

AJ Patel was recovering from a complicated brain surgery when his oncologist burst into the hospital room yelling, “I’ve got some really great news for you!”

For two years, Patel had been going from doctor to doctor trying to diagnose his wheezing, only to be dealt the devastating news that he had stage IV lung cancer and only six months to live. And then they found the brain tumors.

“What are you talking about?” Patel asked. He had never seen an oncologist so happy.

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Mihael Polymeropoulos, Vanda Pharmaceuticals CEO

Phar­ma com­pa­ny con­tin­ues its FDA law­suit spree, this time af­ter agency de­nies fast-track des­ig­na­tion

Vanda Pharmaceuticals is making a name for itself, at least in terms of suing the FDA.

The DC-headquartered firm on Monday filed its latest suit against the agency, with the company raising concerns over the FDA’s failure to grant a fast track designation for Vanda’s potential chronic digestive disorder drug tradipitant, which is a neurokinin 1 receptor antagonist.

Specifically, Vanda said FDA’s “essential point” in its one-page denial letter on the designation pointed to “the lack of necessary safety data,” which was “inconsistent with the criteria for … Fast Track designation.”

Mod­er­na seeks to dis­miss Al­ny­lam suit over Covid-19 vac­cine com­po­nent, claim­ing wrong venue

RNAi therapeutics juggernaut Alnylam Pharmaceuticals made a splash in March when it sued and sought money from both Pfizer and Moderna regarding their use of Alnylam’s biodegradable lipids, which Alnylam claims have been integral to the way both companies’ mRNA-based Covid-19 vaccines work.

But now, Moderna lawyers are firing back, telling the same Delaware district court that Alnylam’s claims can only proceed against the US government in the Court of Federal Claims because of the way the company’s contract is set up with the US government. The US has spent almost $10 billion on Moderna’s Covid-19 vaccine so far.

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Cracks in the fa­cade: Is phar­ma's pan­dem­ic ‘feel good fac­tor’ wan­ing?

The discordant effects of the Covid-19 pandemic on pharma reputation continues. While the overall industry still retains a respectable halo from its Covid-19 quick response and leadership, a new patient group study reveals a different story emerging in the details.

On one hand, US patient advocacy groups rated the industry higher-than-ever overall. More than two-thirds (67%) of groups gave the industry a thumbs up for 2021, a whopping 10 percentage point increase over the year before, according to the PatientView annual study, now in its 9th year.

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Michael Corbo, Pfizer CDO of inflammation & immunology

UP­DAT­ED: Plan­ning ahead for crowd­ed ul­cer­a­tive col­i­tis mar­ket, Pfiz­er spells out PhI­II da­ta on $6.7B Are­na drug

Pfizer has laid out the detailed results behind its boast that etrasimod — the S1P receptor modulator at the center of its $6.7 billion buyout of Arena Pharma — is the winner of the class, potentially leapfrogging an earlier entrant from Bristol Myers Squibb.

Pivotal data from the ELEVATE program in ulcerative colitis — which consists of two Phase III trials, one lasting 52 weeks and the other just 12 weeks — illustrate an “encouraging balance of efficacy and safety,” according to Michael Corbo, chief development officer of inflammation & immunology at Pfizer. The company is presenting the results as a late breaker at Digestive Disease Week.

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Robert Califf (Michael Brochstein/Sipa USA via AP Images)

House Re­pub­li­cans at­tack Chi­na-on­ly da­ta in FDA sub­mis­sions, seek new in­ves­ti­ga­tion in­to re­search in­spec­tions

Three Republican representatives are calling on the FDA to take a closer look at the applications including only clinical data from China.

The letter to FDA commissioner Rob Califf late last week comes as the agency recently rejected Eli Lilly’s anti-PD-1 antibody, which attempted to bring China-only data but ran into a bruising adcomm that may crush the hopes of any other companies looking to bring cheaper follow-ons based only on Chinese data.

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David Mazzo, Caladrius Biosciences CEO

Blam­ing Covid dis­rup­tion, sup­ply short­ages, mi­cro­cap biotech hits the brakes on cell ther­a­py tri­al

More than two years into the Covid-19 pandemic, we’re not done seeing its disruption of biotech.

That’s according to Caladrius execs, who cited the pandemic as one reason for suspending its Phase IIb trial of a cell therapy as a treatment for coronary microvascular dysfunction (CMD). The company plans to go ahead on an interim analysis before deciding what to do with the program, which was built on a licensing deal with Shire in 2018.

Amid mon­key­pox fears, biotechs spring to ac­tion; Mod­er­na’s CFO trou­ble; Cuts, cuts every­where; Craft­ing the right pro­teins; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

It’s always a bittersweet moment saying goodbye, but as Josh Sullivan goes off to new adventures we are grateful for the way he’s built up the Endpoints Manufacturing section — which the rest of the team will now carry forward. If you’re not already, this may be a good time to sign up for your weekly dose of drug manufacturing news. Thank you for reading and wish you a restful weekend.

Co­pay coupons gone wrong, again: Pfiz­er pays al­most $300K to set­tle com­plaints in four states

Pfizer has agreed to pay $290,000 to settle allegations of questionable copay coupon practices in Arizona, Colorado, Kansas, and Vermont from 2014 to 2018.

While the company has not admitted any wrongdoing as part of the settlement, Pfizer has agreed to issue restitution checks to about 5,000 consumers.

A Pfizer spokesperson said the company has “enhanced its co-pay coupons to alleviate the concerns raised by states and agreed to a $30,000 payment to each.”